New drug substances, the result of more than a decade of pharmaceutical research and development, have revolutionized society by saving lives, increasing life-spans, reducing suffering, avoiding surgery, and shortening hospital stays. New breakthroughs in the treatment of non-communicable diseases mean that drug substances are in a constant state of high demand, making the pharmaceutical industry one of the most innovative of industries on the globe. Why then, do so few drugs come to market? It turns out that a key factor is providing drug discovery chemists with tools such as automated flash chromatography to ensure that they can be confident in delivering target compounds in a timely fashion.

The need to accelerate target molecule production

The pharma industry faces numerous challenges in bringing new molecular entities (NMEs) to market. A major challenge is the balance between the costs of pharmaceutical R&D and the NME output. R&D spending is enormous (in the order of $1 billion per NME) and investors, who have rising expectations of receiving a reasonable return on their investments, see the industry as entirely inefficient. They are right. The process is too costly and too slow. In fact, only one in 5,000–10,000 target molecules make it through to become a commercialized drug (1). To put it simply, the longer it takes for discovery research to make target molecules to evaluate as potential drug candidate, the fewer successful molecules will be discovered.

It comes down to the discovery chemist

The success of drug discovery is contingent on the chemist’s productivity and their ability to explore the chemical space and develop optimized target drug candidates. Derek Lowe, an editorially independent blogger for the publishers of Science Translational Medicine (2) addressed this point at the recent BioHub conference, hosted by AstraZeneca in Waltham, MA, USA. He highlighted the need for real change in drug discovery chemistry research and articulated how critical it is for pharma research organizations to find ways to free the organic chemist’s time from irrelevant and mundane tasks often involved with NME synthesis so that they can focus on the search for successful drug candidates. The take-away message was clear: if the industry seeks to bolster its own confidence in the output of their discovery research, focus the chemists only on what truly counts.

Barriers to freeing a discovery chemist’s time

A successful lead compound optimization process minimizes the time between compound ideation and biological testing of that NME. But, chemists know that the process from theoretical target compound through target compound synthesis is far too time-consuming and labor-intensive, regardless of how the chemists multitask.

Synthesis process bottlenecks have frequently been discussed, and include lengthy reaction times, reaction workup, compound purification, solvent evaporation and equipment downtime. However, few recognize that such bottlenecks in the compound synthesis process dramatically amplify delays when one considers the vast number of compounds that must be synthesized and evaluated biologically for any one discovery project. If these bottlenecks are addressed in the process, real gains in practice are possible. Not only will lab productivity improve, but individual chemists will also have more confidence in their ability to quickly deliver target compounds.

What gets in the way of a speedy synthesis workflow?

Longer synthesis workflow cycle times mean fewer discovery projects can be advanced within a given timeframe, resulting in sub-optimal production of test compounds. Discovery chemists want to be more efficient in synthesis and employ numerous tools (some automated) to speed up the process. However, labs with high productivity are rare.

Sometimes chemists find that certain automated equipment is difficult to master, lacks productivity-improving features, or is even unreliable, which can have major consequences. Firstly, equipment failure during critical steps (such as purification with flash column chromatography) risks the loss of target compounds that have taken days or weeks to synthesize. This is an intolerable risk for chemists and wastes precious time to remake the compound. Secondly, when equipment fails chemists need to deal with the downtime and this can have a major impact on their workflow, especially if the equipment is open-access (commonly used by any of the lab’s chemists). If vendor service is required, this can take time to coordinate and can be a real hassle for chemists to manage.

Building confidence with reliable workflow tools

In practice, I have learned that increasing workflow efficiency can decrease synthesis workflow cycle time by 80% or more. Some may be skeptical, but CRO leaders supporting their client partners in discovery chemistry recognize that halving the workflow cycle time also cuts the cost (and time) of synthesizing a target molecule in half. Sounds great, right? But how does one translate this goal into practical application within synthesis workflows?

The first step in improving workflow efficiency is to make smart choices when selecting laboratory tools from a vendor that stands behind their products. Choose a solutions vendor that focuses on the needs of organic chemists by providing entire synthesis workflow support, provides robust, intelligent solutions and behaves like a partner. In science, a vendor should be a partner with technically competent sales and service staff that have in-the-trenches know-how and can help chemists operate efficiently. And, because they have walked-the-walk, a partner’s expert applications staff work to create solid, turnkey system solutions with intelligent features that simplify the workflow and also provide support with hands-on training in how to optimize the solution’s performance. The outcome will be more uptime, reduced support costs and a greater confidence that target compounds can be delivered rapidly and reliably to advance the drug discovery project.

The next article in this series describes how reliable flash column chromatography can help you to purify your target compounds with confidence and actually accelerate drug discovery.